Treatment of polycythemia vera (PV) aims to maintain hematocrit on target to reduce risk of thrombotic complications, while preventing disease progression to myelofibrosis (MF) and acute myeloid leukemia (AML). This analysis evaluated cost-effectiveness of adding ropeginterferon alfa-2b (ropegIFNα) to phlebotomy in patients with low-risk PV (those younger than 60 years without prior thrombosis), compared to phlebotomy alone. We combined a 12-month decision tree with a semi-Markov cohort model comparing ropegIFNα to the standard treatment from the Austrian healthcare system perspective over 30 years. Outcomes were quality adjusted life years (QALYs), costs, and incremental cost-utility ratio (ICUR). Model inputs were obtained from the phase 2 Low-PV study, additional published literature and from Austrian-specific cost databases. One-way and probabilistic sensitivity analyses (SA) assessed the robustness of findings. RopegIFNα led to 1,43 higher QALYs and 50.960 EUR overall higher costs compared to phlebotomy alone, with an ICUR of 35.525 EUR/QALY. Thrombosis, MF, and AML costs decreased for the ropegIFNα group by 12%, 30% and 16% respectively, due to the delayed complications onset and disease progression. In the one-way SA, ropegIFNα costs and discount rates had the greatest impact on results. The probabilistic SA showed a 100% probability of cost-effectiveness at willingness-to-pay threshold aligned to the Austrian GDP per capita. RopegIFNα is a cost-effective treatment option for patients with low-risk PV. These findings suggest that early treatment with ropegIFNα could ensure optimal resource allocation by preventing costly thrombotic events and progression to MF whilst increasing patient quality of life.